TMEM16 Proteins Produce Volume-regulated Chloride Currents That Are Reduced in Mice Lacking TMEM16A

Almaca, Joana and Tian, Yuemin and Aldehni, Fadi and Ousingsawat, Jiraporn and Kongsuphol, Patthara and Rock, Jason R. and Harfe, Brian D. and Schreiber, Rainer and Kunzelmann, Karl (2009) TMEM16 Proteins Produce Volume-regulated Chloride Currents That Are Reduced in Mice Lacking TMEM16A. JOURNAL OF BIOLOGICAL CHEMISTRY, 284 (42). pp. 28571-28578. ISSN 0021-9258, 1083-351X

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Abstract

All vertebrate cells regulate their cell volume by activating chloride channels of unknown molecular identity, thereby activating regulatory volume decrease. We show that the Ca2+-activated Cl- channel TMEM16A together with other TMEM16 proteins are activated by cell swelling through an autocrine mechanism that involves ATP release and binding to purinergic P2Y(2) receptors. TMEM16A channels are activated by ATP through an increase in intracellular Ca2+ and a Ca2+-independent mechanism engaging extracellular-regulated protein kinases (ERK1/2). The ability of epithelial cells to activate a Cl-conductance upon cell swelling, and to decrease their cell volume (regulatory volume decrease) was dependent on TMEM16 proteins. Activation of I-Cl,I-swell was reduced in the colonic epithelium and in salivary acinar cells from mice lacking expression of TMEM16A. Thus TMEM16 proteins appear to be a crucial component of epithelial volume-regulated Cl-channels and may also have a function during proliferation and apoptotic cell death.

Item Type: Article
Uncontrolled Keywords: ASCITES TUMOR-CELLS; ANION CHANNELS; DECREASE; CALCIUM; CONDUCTANCE; CAMP; PROLIFERATION; STIMULATION; INHIBITION; ACTIVATION;
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann
Depositing User: Dr. Gernot Deinzer
Date Deposited: 03 Sep 2020 07:02
Last Modified: 03 Sep 2020 07:02
URI: https://pred.uni-regensburg.de/id/eprint/28265

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